Department of Pharmacology, All India Institute of Medical Sciences-Bhopal, Madhya Pradesh 462020, India.
Department of Pharmacology, All India Institute of Medical Sciences-Bhopal, Madhya Pradesh 462020, India.
J Affect Disord. 2024 Dec 15;367:832-844. doi: 10.1016/j.jad.2024.09.041. Epub 2024 Sep 10.
Currently, 30-50 % of individuals with depression and 40 % with anxiety-collectively referred to as common mental disorders (CMDs), exhibit inadequate responses to antidepressant treatments.
To assess the effectiveness and safety of drug-metabolizing enzyme pharmacogenetic variation informed treatment (PGxIT) versus usual antidepressant treatment (UT) in patients with CMDs.
A literature search was conducted in the MEDLINE, Scopus, and Cochrane Library databases from inception until January 30, 2024.
Studies were selected based on CMD diagnoses, reporting on the genetic variations of drug-metabolizing enzyme (DME) genes in relation to antidepressants, involving PGxIT and UT groups with human subjects, and published in English.
Data extraction and quality assessment were performed independently by two authors. A pooled risk ratio (RR) with 95 % CI was estimated using both random and fixed-effect models, and heterogeneity was assessed using Cochran's Q test and the I statistic. The publication bias of eligible studies was assessed using post hoc Doi plots and the LFK index.
This systematic review included 18 studies (n = 7021). The PGxIT demonstrated greater efficacy in the remission of symptoms of depressive disorder at 8 weeks (RR 1.523 [95 % CI: 1.255-1.843]; I = 48 %) and 12 weeks (RR 1.631 [95 % CI: 1.001-2.657]; I = 86 %; p < 0.01), and symptoms of anxiety disorder compared to UT. Additionally, the risk of adverse drug events (ADEs) was significantly lower in the PGxIT group (RR = 0.65 [95 % CI: 0.52-0.82]; I = 0 %) than in the UT group. The certainty of evidence for both outcomes was moderate.
This systematic review and meta-analysis suggest that pharmacogenetically guided antidepressant treatment, based on genetic variation in drug-metabolizing enzymes, is associated with superior efficacy in the remission of symptoms for patients with depressive disorders and a reduction in ADEs compared to usual treatment and the findings of the systematic review for remission in anxiety disorders indicate that, PGx guided treatment is also associated with increased remission of symptoms in anxiety disorders compared to usual treatment.
目前，30-50%的抑郁症患者和 40%的焦虑症患者——统称为常见精神障碍（CMD），对抗抑郁药物治疗的反应不足。
评估药物代谢酶药物基因组学变异指导治疗（PGxIT）与常规抗抑郁治疗（UT）在 CMD 患者中的疗效和安全性。
从开始到 2024 年 1 月 30 日，在 MEDLINE、Scopus 和 Cochrane 图书馆数据库中进行了文献检索。
根据 CMD 诊断，选择报告与抗抑郁药相关的药物代谢酶（DME）基因遗传变异的研究，涉及 PGxIT 和 UT 组的人体受试者，并以英文发表。
两位作者独立进行数据提取和质量评估。使用随机和固定效应模型估计了具有 95%置信区间的合并风险比（RR），并使用 Cochran Q 检验和 I 统计量评估了异质性。使用事后 Doi 图和 LFK 指数评估合格研究的发表偏倚。
本系统评价包括 18 项研究（n=7021）。PGxIT 在 8 周（RR 1.523 [95%CI：1.255-1.843]；I=48%）和 12 周（RR 1.631 [95%CI：1.001-2.657]；I=86%；p<0.01）时，以及焦虑症症状的缓解方面显示出更高的疗效与 UT。此外，与 UT 组相比，PGxIT 组的药物不良事件（ADE）风险显著降低（RR=0.65 [95%CI：0.52-0.82]；I=0%）。这两个结果的证据确定性为中等。
本系统评价和荟萃分析表明，基于药物代谢酶遗传变异的药物基因组学指导的抗抑郁治疗与抑郁症患者症状缓解的疗效提高和与常规治疗相比，不良药物事件（ADE）的减少有关，并且系统评价对焦虑症缓解的结果表明，PGx 指导治疗与常规治疗相比，也与焦虑症症状缓解的增加有关。
